title: Antifungal property of hibicuslide C and its membrane-active mechanism in Candida albicans.
abstract: In this study, the antifungal activity and mode of action(s) of hibicuslide C derived from Abutilon theophrasti were investigated. Antifungal susceptibility testing showed that hibicuslide C possessed potent activities toward various fungal strains and less hemolytic activity than amphotericin B. To understand the antifungal mechanism(s) of hibicuslide C in Candida albicans, flow cytometric analysis with propidium iodide was done. The results showed that hibicuslide C perturbed the plasma membrane of the C. albicans. The analysis of the transmembrane electrical potential with 3,3'-dipropylthiacarbocyanine iodide [DiSC3(5)] indicated that hibicuslide C induced membrane depolarization. Furthermore, model membrane studies were performed with calcein encapsulating large unilamellar vesicles (LUVs) and FITC-dextran (FD) loaded LUVs. These results demonstrated that the antifungal effects of hibicuslide C on the fungal plasma membrane were through the formation of pores with radii between 2.3 nm and 3.3 nm. Finally, in three dimensional flow cytometric contour plots, a reduced cell sizes by the pore-forming action of hibicuslide C were observed. Therefore, the present study suggests that hibicuslide C exerts its antifungal effect by membrane-active mechanism.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-ku, Daegu 702-701, Republic of Korea.
authors.forename: Ji Hong
authors.initials: JH
authors.lastname: Hwang
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Jin
authors.forename: Eun-Rhan
authors.initials: ER
authors.lastname: Woo
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D052160:Benzothiazoles; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002232:Carbocyanines; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002463:Cell Membrane Permeability; D003911:Dextrans; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D019660:Malvaceae / Q000737:chemistry*; D008564:Membrane Potentials / Q000187:drug effects; D010666:Phenylpropionates / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry*; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D052160:Benzothiazoles; D002232:Carbocyanines; D003911:Dextrans; D005452:Fluoresceins; D005456:Fluorescent Dyes; D010666:Phenylpropionates; D010936:Plant Extracts; D053835:Unilamellar Liposomes; C015219:fluorescein isothiocyanate dextran; C000595664:hibicuslide C; C012944:3,3'-dipropyl-2,2'-thiadicarbocyanine; D000666:Amphotericin B; D016650:Fluorescein-5-isothiocyanate; C007740:fluorexon
keywords: 3,3′-dipropylthiacarbocyanine; 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; ATCC; American Type Culture Collection; Antifungal effect; CH(2)Cl(2); CLSI; Candida albicans; Clinical and Laboratory Standards Institute; DiSC(3)(5); EtOAc; FD; FITC; FITC–dextran; Hibicuslide C; KCTC; Korean Collection For Type Cultures; LUV; MIC; MTT; MeOH; Membrane-active mechanism; PBS; PC; PE; PI; Phytochemical; dichloromethane; ethyl acetate; fluorescein isothiocyanate; large unilamellar vesicle; methanol; minimum inhibitory concentration; phosphate buffered saline; phosphatidylcholine; phosphatidylethanolamine; phosphatidylinositol